The metastable radioisotope 99mTc, which results from the radioactive decay of 99Mo, is used in over 20 million nuclear medicine procedures performed annually in the United States. 99mTc is especially useful for such procedures because it can be chemically incorporated into small molecule ligands and proteins that concentrate in specific organs or tissues when injected into the body, enabling a variety of clinical diagnostic and therapeutic applications. The isotope has a half-life of about six hours and emits a 143 keV gamma that can be efficiently detected by scintillation cameras. This short half-life also reduces the amount of time the isotope resides in the body and minimizes radiation dose to other undiseased parts of the body.
99mTc is currently produced through a multistep process that begins with the neutron irradiation of fissile 235U contained in uranium-bearing targets to produce 99Mo in a nuclear reactor. Following irradiation, the targets are chemically processed to separate 99Mo from other fission products, including 131I and 133Xe. The separated 99Mo, which is contained in a solution, is then adsorbed onto an alumina (Al2O3) column that is contained in small cylinders. The columns are shipped to radiopharmacies and hospitals in radiation-shielded technetium generators. The 99mTc is typically recovered from the generator by elution of the column with a saline solution. A technetium generator can be eluted several times a day for about a week before it needs to be replaced with a fresh generator. However, because of its relatively short 66-hour half-life, 99Mo cannot be stockpiled for use. It must be made on a weekly or more frequent basis to ensure continuous availability. Therefore, any interruption in the production, transport, or delivery of 99Mo or technetium generators can have substantial impacts on patient care.
Nuclear reactors provide an efficient source of low-energy neutrons for 99Mo production from fission in 235U-bearing targets. The amount of 99Mo produced in a target is a function of irradiation time, the thermal neutron fission cross section for 235U, the thermal neutron flux on the target, the mass of 235U in the target, and the half-life of 99Mo. The target must be properly sized to fit into the irradiation position inside the reactor, contain a sufficient amount of 235U to produce the required amount of 99Mo when it is irradiated (approximately 6% of the 235U fission fragments are 99Mo atoms), have good heat transfer properties to prevent overheating and target failure during irradiation, provide a barrier to the release of radioactive products, especially fission gases, during and after irradiation, and comprise target materials that are compatible with the chemical processing steps that are used to recover and purify 99Mo from the irradiated target. Targets can typically be shaped as plates, pins, or cylinders and be made of uranium metal, uranium oxides, or uranium alloys. The fissionable material is typically encapsulated in a cladding to protect the chemically reactive uranium metal or alloy and to contain the fission products produced during irradiation.
Currently, the vast majority of 99Mo produced in the world is by the irradiation of highly enriched uranium targets (HEU, ˜93% 235U). Driver reactor cores operating at tens to hundreds of megawatts produce a high neutron flux in an irradiation region where targets, using HEU as fuel, are irradiated continuously for about a week to achieve near-maximum 99Mo production in the targets while meeting quality requirements. Irradiation times must be short (7 to 21 days) to control quality in purity levels and specific activity. After irradiation, the targets are transferred and processed at a hot cell facility to separate the 99Mo product isotope. The waste stream, including the uranium, is then stored for decay and disposed of at a later date. Currently, target fuel is not reprocessed.
HEU irradiation gives the highest production efficiency and the lowest mass of waste materials to store and to ultimately dispose. However, the use of HEU raises concerns about nuclear proliferation and, therefore, the continued availability of HEU for 99Mo production. In particular, nonproliferation security issues are pressuring a change from HEU to low enriched uranium (LEU, less than about 20% 235U) for reactors and targets. However, the use of LEU introduces more difficulty in irradiation, processing, and radioactive waste management and may lead to serious reactor and target issues. For example, fuel replacement may not be compatible with balance of plant and use of LEU may require more irradiation space for increased target mass and target cooling. The change from HEU to LEU may also raise process and quality issues, such as increased uranium process and waste mass, and increased α-emitter production can become a problem for long irradiation times and/or hard spectrum systems. See “Medical Isotope Production without Highly Enriched Uranium,” National Research Council (2009).
The current fleet of nuclear reactors throughout the world that produce 99Mo from the fission process are aging and cannot meet the world demand. Further, the current high-flux reactors used for production are owned by government agencies or universities and are not operated for the sole purpose of producing 99Mo. Therefore, the true cost for the production of 99Mo becomes difficult to ascertain since these reactors are subsidized in the costs of operation, maintenance, and refueling. Further, the demands of other customers, in addition to the production of 99Mo, cause conflicts in scheduling of these multi-use reactors.
There is clearly a need for a domestic (U.S.) supply of 99Mo/99mTc for the nation's medical community. Current 99Mo consumption in the U.S. is about 6000 six-day Curies (Ci) per week. Production of 6,000 six-day Ci per week requires at least 1.1 MW of continuous target fission power, assuming two post-irradiation days for processing and shipping. The U.S. has depended on imports primarily from Canada which, except for a few short interruptions, have been quite reliable in the past. The National Research Universal (NRU) reactor at Chalk River, Canada is used to irradiate targets containing HEU. However, recently this source has become unreliable, due to planned and unplanned outages and aging reactors. In the U.S., there has been no domestic supply of 99Mo since Cintichem operations ceased in the late 80's. In the mid 90's the Department of Energy (DOE) undertook an effort to provide a domestic supply of 99Mo to be used, primarily, as a back-up to the Canadian supply. However, in anticipation of the Canadian Maple reactors, the DOE effort was terminated in the late 90's. Unfortunately, the Maple reactors effort was plagued with licensing and technical problems, and was therefore terminated in 2008. Therefore, there currently is no domestic or long-term backup supply for 99Mo production.
The most cost effective approach to meeting the domestic 99Mo demand is to construct a reactor system and an adjacent chemical processing facility whose sole purpose is the production of medical isotopes. Therefore, a need remains for a simple straightforward reactor and facility design concepts that can satisfy all requirements and constraints for production of sufficient 99Mo to meet domestic U.S. demand using low-enriched uranium fuel.